A. Field of the Invention
This invention relates to a film which is applied to the wet mucosa of the oral cavity and a preparation comprising the same, which are useful to maintain a long-term intraoral administration of a drug.
B. Description of the Related Art
Known dosage forms for intraoral administration of drugs include solutions, ointments, troches, buccal tablets, sublingual tablets, etc. Recently, slow-releasing intraoral tablets of track-field type which are less causative of an adverse feeling in the oral cavity (as described in JP-A-55-59-09, JP-A-58-154547, and JP-A-58-154548, the term "JP-A" as used herein means an "unexamined published Japanese patent application") and slow-releasing Nifedipine tablets of track-field type applied to the oral mucosa (as described in JP-A-61-15829 and JP-A-61-17510) have been proposed. For the purpose of further reducing an adverse feeling in the oral cavity, medical bandage using, as a base, a water-soluble high polymer which exhibits adhesion when dissolved or gelled with water (as described in JP-A-60-142927), preparations applicable to the oral mucosa comprising a water-soluble film having incorporated thereinto a steroid or non-steroid agent (as described in JP-A-61-280423), and sheet preparations comprising a support sheet having thereon a drug, gelatin, agar, gluten, a carboxyvinyl polymer, a polyhydric alcohol, a gum, and a wax as essential components (as described in JP-A-61-85315) have also been proposed.
More recently, there have been proposed bases for application to the oral mucosa which comprise a mixture of a water-soluble substance and a water-insoluble substance; for example, intraoral bandage composed by a soft film in which at least one of a polycarboxylic acid and a polycarboxylic acid anhydride, and a vinyl acetate polymer are mixed in a compatible state as disclosed in JP-A-61-249472 and JP-A-61-249473; a base comprising a water-insoluble or sparingly water-soluble support having thereon an adhesive layer containing an acrylic acid polymer which exhibits adhesion when dissolved in or swollen with water and a water-insoluble cellulose derivative as disclosed in JP-A-63-160649; a composite for application to the oral mucosa comprising a surface layer containing ethyl cellulose and a vinyl-pyrrolidone polymer or copolymer having thereon an adhesive layer as disclosed in JP-A-63-171564 and JP-A-63-171565; and an adhesive composition containing a vinylpyrrolidone polymer or copolymer, at least one of hydroxyethyl cellulose and hydroxypropyl cellulose, and a water-retaining softener as disclosed in JP-A-63-174660.
However, none of these known intraoral preparations or bases satisfies both duration of adhesion and freedom from an adverse feeling in the oral cavity on use. For example, since solutions, ointments or the like preparations easily run away with saliva or other water content, it is difficult to maintain efficacy for a long time with these preparations. Troches, which are large tablets prepared by punching a mixture of a drug and a base, e.g., saccharides, cause a considerable adverse feeling. Buccal tablets and sublingual tablets are generally designed for rapid mucosal absorption of drugs and are, therefore, of short duration. The track-field type tablets, though slowly releasing a drug, have a thickness as large as 1.3 to 3 mm and lack softness, still involving the problem of an adverse feeling on use. The preparations for application to the oral mucosa comprising a water-soluble film containing a drug have softness and thereby cause a reduced adverse feeling in the oral cavity. However, since the film base is water-soluble, it is easily dissolved in saliva or water contents in the oral cavity and is, therefore, poor in duration of efficacy. The bases comprising a mixture of a water-soluble substance and a water-insoluble substance are soft and less causative of an adverse feeling upon use. Also, they take time to disappear in the oral cavity and are thus expected to have a longer duration of pharmaceutical effects as compared with bases comprising a water-soluble substance alone. These bases nevertheless exhibit adhesion only for 2 to 10 hours at the longest.
Hence, an intraoral preparation satisfying all the three requirements, i.e., freedom from an adverse feeling in the oral cavity on use, excellent shape retention on water absorption, and long-term adhesion to the wet oral mucosa, has not yet been developed.